For 25 years, the Diabetes Research Center (DRC) of the Joslin Diabetes Center, with its Core Laboratories, Enrichment Program and support for Pilot and Feasibility (P&F) studies, has played a major role in fostering expansion in the scope and intensity of diabetes research at Joslin and Harvard Medical School. The DRC has provided essential infrastructure for basic, translational, and clinical research. During the last five year, Joslin DRC investigators have generated ground-breaking research aimed at understanding the pathogenesis of diabetes and its complications. These advances have been critically dependent upon the continually evolving cutting-edge technology and synergy of our DRC Cores. The current revised application builds upon these strengths and adds new and innovative components to the DRC. We propose to establish a Regional Resource Core at Boston University to enhance our capacity in computational biology that will allow us to move forward with next-generation sequencing and the other complexities of data management. The Boston University Joslin Regional Computational (BUJRC) Core will be accompanied by an expansion of the P&F Program, also at Boston University. For the Joslin-based Cores we propose a new DRC IPS Core. Clearly, IPS cells provide an extraordinary opportunity to study the pathogenesis of diabetes and its complications. Joslin is uniquely positioned to move forward because of its well-characterized patient populations and our close ties with the Harvard Stem Cell Institute. The new requirements for data generation have provided the opportunity to develop a new Advanced Genomics and Genetics Core, based on our previously distinct Genomics and Genetics Cores. The Advanced Microscopy Core, the Animal Physiology Core and the Flow Cytometry Core have all acquired sophisticated new equipment with substantial support from Joslin, and the new major award from State of Massachusetts resulting in a variety of new services. The P&F study program has been very successful in supporting young investigators and innovative research at Joslin and other Harvard institutions. The Enrichment Program continues to enhance the research environment for students, postdoctoral fellows and investigators by supporting a valuable array of academic exercises and visiting speakers.